The present invention relates to a process for microencapsulation of hydrophilic core materials utilizing interfacial polycondensation techniques.
The encapsulation of core substances by interfacial polycondensation has been widely used in the pharmaceutical, agricultural, dye, paint, and carbonless paper industries. Microencapsulation is a process whereby small particles of core materials such as liquids, solids, solutions, or dispersions are thinly coated by a separate material. Microencapsulation is often used to improve certain physical characteristic of formulations such as compressibility and flow. In addition, microencapsulation has been utilized to modify chemical release, to improve chemical stability, and to permit the mixing and storage of reactive or incompatible materials.
The principle of the microencapsulation method lies in bringing into contact a first liquid phase containing the core material to be encapsulated and a polycondensation reagent, with another liquid phase which is immiscible with the first phase and contains a second reagent capable of reacting with the first to give a polycondensation product. When the two phases are brought into contact, the two condensation reagents react at the interface of the phases, and by polycondensation, a wall of polymer forms around the drops of liquid core materials. The capsules obtained can then be washed and dried before use.
Various particular methods for carrying out this general technique have been proposed. One method consists of carrying out the dispersion and reaction simultaneously. For example, in a first stage, an aqueous phase is prepared which contains the core substance to be encapsulated generally dissolved in a solvent together with a hydrophilic polycondensation reagent. This first phase is then dispersed in an organic phase containing a hydrophobic polycondensation reagent. In this technique, the polycondensation reaction takes place at the actual moment of dispersion. Because the polycondensation and dispersion reactions occur simultaneously, microcapsules having an excessively wide distribution of diameters result.
In order to overcome this disadvantage, another technique features carrying out the process in two stages so as to separate the dispersion operation from the polycondensation reaction. For example, U.S. Pat. No. 3,522,346 to Chang, provides a process of encapsulating aqueous core substances in microcapsules having controlled size, thickness, and permeability. Droplets of an aqueous phase containing the core substance to be encapsulated together with the hydrophilic polycondensation reagent are dispersed in an organic phase. Next the hydrophobic polycondensation reagent is added to the dispersion thereby producing a polymerized microcapsule by interfacial condensation.
Initially polymer formation is rapid. However after the initial membrane is deposited, further polymerization is limited by the rate of diffusion of the hydrophilic polycondensation reactant into the organic solvent. Unfortunately as a consequence many of the microcapsules formed by this method are not easily recovered as a dry powder and tend to coalesce to form larger aggregates. Moreover, the encapsulated core substances are generally limited to anionic substances due to pH constraints of the aqueous phase.
In the utilization of interfacial polymerization techniques to encapsulate hydrophilic core materials, a particularly serious limitation has been encountered in the types of materials that are amenable to encapsulation. Specifically, the polycondensation monomer included in the aqueous phase poses certain pH constraints which affect the interfacial partitioning and pH stability of the selected core material to be encapsulated. For example, microencapsulation of quaternary drugs such as methantheline bromide and benzalkonium chloride has been heretofore generally unsuccessful. Further, microencapsulation of xanthine drugs and cationic drugs has generally resulted in low yield of encapsulated drug generally due to partitioning of the drug into the organic phase. In some instances degradation of the core material is observed and may be attributed to the pH conditions of the core influenced by residual monomer in the aqueous phase after polymerization is complete.
The problems discussed above can generally be attributed to the polycondensation monomer included in the aqueous phase to be microencapsulated. If the pH of the aqueous core can be controlled, then a much greater control over drug solubility, partitioning and stability can be established for the particular core material to be encapsulated. The present invention provides a process for microencapsulating a hydrophilic core material which overcomes many of the problems encountered with prior methods.